Deep Vein ThrombosisA Case for Early Intervention

Hiranya A. Rajasinghe MD

Vascular and Endovascular Surgery

Naples, Florida

Mainstream RxClot removal is not a part of recommendation for care

Clot removal is not a part of recommendation for care

2004

Acute Venous ThromboembolismAcute Venous Thromboembolism

AnticoagulationAnticoagulation

Calf DVT Calf DVT

…. for everyone! …. for everyone!

Femoral-popliteal Femoral-popliteal Iliofemoral Iliofemoral

Do not recognize iliofemoral DVT as a unique conditionDo not recognize iliofemoral DVT as a unique condition

……Change occurred in the 2008 guidelines…Change occurred in the 2008 guidelines…

Acute DVTAcute DVT

Where are We Going…

• Surgeon General’s “Call to Action”– Joint Commission/NQF Mandates

• DVT/PE Risk Assessment Protocols 2008– Prevention– Intervention

• ACCP Recommendations Changing 2008– Thrombolytic Therapy

• Iliofemoral

• SIR Recommendations– Thrombolytic Therapy

• Iliofemoral

• This joint effort elevates the awareness of DVT to a National healthcare level.

• This joint effort recognizes the need to standardize the care of DVT patients and measure outcomes.

• The American College of Chest Physicians (ACCP) will publish the physician consensus on patient treatment.– It is changing its 2004 DVT treatment guidelines

• 2007 guidelines will include a thrombolysis recommendation• 2007 guidelines will include a recommendation for

specifically treating iliofemoral DVT (CDT, PMT) (Comerota)

Why is this Information Important ?

6

PE600,00

0

Silent PE1

Million

DVT2

Million

Death

200,000Estimated Cost of VTE Care $1.5 Billion/yearEstimated Cost of VTE Care $1.5 Billion/year

VTE: A Public Health ProblemEstimated Annual Incidence

Post-Thromboti

c Syndrome800,000

Pulmonary Hypertensi

on30,000

Goldhaber. . LancetLancet 1999;353:1386-1389 1999;353:1386-1389

What is a DVT?

• Blood clot in a deep vein• Blocks blood from returning

to heart• Damages the valves and

vein wall• Potentially grow or travel

VEIN

Virchow’s Triad

StasisStasisAir Travel, Obesity, Air Travel, Obesity,

ImmobilityImmobility

Endothelial InjuryEndothelial InjuryLimb Trauma, Major SurgeryLimb Trauma, Major Surgery

HypercoagulabilityHypercoagulabilityBCP, Cancer, HereditaryBCP, Cancer, Hereditary

DVT Risk Factors and Symptoms

Risk Factors

• Immobility, such as bed rest or sitting for long periods

• Previous DVT or family history of DVT

• Recent surgery • Above the age of 40 • Hormone therapy or oral

contraceptives • Pregnancy or post-partum • Previous or current cancer • Limb trauma and/or orthopedic

procedures • Coagulation abnormalities • Obesity

Symptoms

• Pain

• Discoloration of the legs

• Calf or leg pain or tenderness

• Swelling of the leg or lower limb

• Warm skin

• Surface veins become more visible

• Leg fatigue

Economy Class Syndrome

• Flights over 4 hours

• Any prolonged trip in cramped conditions

• Immobility and dehydration

• Prevention:– aspirin, fluids, avoid alcohol, frequent walks,

support stockings

Symptoms

• Commonly no symptoms!• Pain• Swelling• Redness• Palpable clot

Diagnosis• Clinical: exam and

symptoms

• Venous duplex

• Magnetic resonance venography

• Blood test:

Elevated D-dimer

DVT treatments

• MEDICAL – Anticoagulation (blood thinning medications)

• IV Heparin (in hospital only)• Low molecular weight heparin (given at home)• Coumadin (by mouth)

– Support Stockings– Elevation

Therapeutic Goals of DVT Treatment

• Relieve Patient Symptoms• Prevent Pulmonary Embolism• Prevent Further Thrombus Propagation• Prevent DVT Recurrence• Maintain Valve Competence• Prevent Postthrombotic Syndrome

Complications of DVT

• Pulmonary Embolus

• Post-DVT syndrome

Pulmonary Embolus

• Clot travels to lungs• Blocks lung artery• Frequently fatal• Symptoms:

– chest pain – shortness of breath– or death

Vena Cava Interruption: IVC Filters

Indications:

Prevent large emboli from reaching the lungs

Contraindication for anticoagulation therapy

Complications while receiving anticoagulation therapy

High risk of mortality from recurrent PE

Placement:

Below renal veins

Inserted via jugular or femoral vein

May be easily removed

Caval Filters

• PERMANENT• RETRIEVABLE

What We Know…

• Gold Standard –Anticoagulation

• Heparin, Lovenox, Coumadin

–Compression Hose

• Long Term Results–Anticoagulation

• Prevents Clot from Propagating – Does not dissolve thrombus

• PE Prevention

– May Lead to Post Thrombotic Syndrome

Current Standard Therapy for DVT:Anticoagulation Therapy

• Relies on the patient’s fibrinolytic system for thrombolysis– Veins have limited capacity to dissolve thrombus– Only 6% of patients with acute proximal DVT show complete lysis of

thrombus within 10 days– Recurrent thrombosis and postthrombotic syndrome have been highly

correlated to residual thrombus

• Anticoagulation does not directly resolve symptoms– Leg edema, pain and difficulty ambulating associated with DVT usually

subside over days to weeks as collateral venous channels develop– Many patients continue to experience some degree of venous

obstructive symptoms, especially during exercise

Breddin HK et al. Effects of LMWH on thrombus regression and recurrent thomboembolsim in patients with DVT. N Engl J Med. 2001

Sherry S. Thrombolytic Therapy for Deep venous thrombosis. Semin Intervent Radiol 1985

Post-DVT Syndrome

• Reversed flow of blood in veins

• Symptoms:

pain, swelling, ulceration

• 6-7 million patients with venous stasis changes

• 500,000 patients with leg ulcers yearly

Valvular Damage

Venous Blood Flow• The Low pressure of the venous system

requires special adaptations to help return blood to the heart.

• A complex system of venous valves, the calf muscle pump, and the respiratory pump all assist in returning blood to the heart.

• Venous valves are one way valves of hinge-like flaps formed by the Tunica Intima– Most abundant in the lower limbs where gravity

opposes flow.– Prevent backflow as blood travels toward the

heart.

Calf muscle pump

Pathophysiology of Postthrombotic Syndrome

• Acute thrombus, inflammation, and the process of vein recanalization cause valvular reflux

• Reflux and/or chronic obstruction causes venous hypertension which leads to edema, tissue hypoxia, or ulceration

• Clinical studies suggest that reflux in proximal veins is associated with the manifestation of Postthrombotic Syndrome

Kahn et al. Relationship between deep venous thrombosis and the

postthrombotic syndrome. Arch Intern Med. 2004

Postthrombotic Syndrome (PTS)

• 29-47% of DVT patients eventually develop PTS (Prandoni, Brandjes, Kahn)*

• 25-33% of Patients with PTS will develop severe symptoms such as ulcers and skin deterioration (Kahn)

• 75% of the cost of Treating DVT is related to PTS (Kahn, Berqvist)

• 6% of home care clientele and 18% of expenditures are related to PTS (Kahn)

Frequency of PTS with symptomatic DVT (Prandoni)

Follow up Incidence

1 Year 17%

2 Years 23%

5 Years 28%

8 Years 29%

Frequency of PTS with symptomatic DVT (Brandjes)

5 years 47%

Frequency of PTS with symptomatic DVT (Ginsberg)

1 Year 27%

Postthrombotic SyndromeSigns & Symptoms

Signs• Edema• Stasis • Dermatitis• Redness• Dependent Cyanosis• Varicose Veins• Venous dilation• Open Ulcer• Hyperpigmentation• Healed Ulcer

Symptoms• Heaviness• Cramps• Pain• Paresthesia• Swelling• Bursting Pain• Itching

Long-Term Follow-Up• 59 patients with iliofemoral DVT• Conventional anticoagulation• Followed 5 years

Long-Term Follow-Up• 59 patients with iliofemoral DVT• Conventional anticoagulation• Followed 5 years

Anticoagulation

Iliofemoral DVTIliofemoral DVT

Akesson H, Eur J Vasc Surg 1990

Delis K T et alAnn Surg 2004;239(1):116

Akesson H, Eur J Vasc Surg 1990

Delis K T et alAnn Surg 2004;239(1):116

Parameter @ 5 yrs %Calf muscle dysfunction 50%

Ambulatory venous hypertension 95%

Venous insufficiency 90%

Venous claudication 15% -45%

Venous ulceration 15%

Limited ambulation 15%

Reduced QOL nearly all

Parameter @ 5 yrs %Calf muscle dysfunction 50%

Ambulatory venous hypertension 95%

Venous insufficiency 90%

Venous claudication 15% -45%

Venous ulceration 15%

Limited ambulation 15%

Reduced QOL nearly all

Anticoagulation

Iliofemoral DVTIliofemoral DVT

Akesson H, Eur J Vasc Surg 1990

Delis K T et alAnn Surg 2004;239(1):116

Akesson H, Eur J Vasc Surg 1990

Delis K T et alAnn Surg 2004;239(1):116

Risk of Recurrence

1,149 Symptomatic DVT Rx’ed with Anticoagulation

1,149 Symptomatic DVT Rx’ed with Anticoagulation

Iliofemoral DVTIliofemoral DVT

Overall recurrence @ 3 mos – 5.1%Femoral vein thrombosis – 5.3%

Iliofemoral DVT – 11.8%

Overall recurrence @ 3 mos – 5.1%Femoral vein thrombosis – 5.3%

Iliofemoral DVT – 11.8%

Douketis JD et alAm J Med 2001;110:515

Douketis JD et alAm J Med 2001;110:515

ResultsResults

Risk for RecurrenceRisk for RecurrenceFactorFactor Odds RatioOdds Ratio

Iliofemoral DVT 2.4Cancer 2.6Iliofemoral DVT 2.4Cancer 2.6

Time after Initial DVT, moTime after Initial DVT, mo

Cu

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lativ

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rop

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Pa

tient

s w

ith R

ecu

rre

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TE

Cu

mu

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ith R

ecu

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TE Hazard ratio 2.9 with

residual thrombus P = 0.001

Hazard ratio 2.9 with residual thrombus P = 0.001

Residual Venous Thrombus

Recurrent DVTRecurrent DVT

Prandoni, P et alAnn Intern Med 2002;137:955

Prandoni, P et alAnn Intern Med 2002;137:955

Residual thrombus predictive of recurrent DVTResidual thrombus predictive of recurrent DVT

Increasing evidence…

• Early thrombus resolution is associated with improved outcome!

Increasing evidence…

• Early thrombus resolution is associated with improved outcome!

(especially iliofemoral DVT)(especially iliofemoral DVT)

…and…

• Without thrombus removal, risk of recurrence is increased

…and…

• Without thrombus removal, risk of recurrence is increased

Acute DVTAcute DVT

Early Intervention = Reduction of Postthrombotic

Syndrome• Early thrombus removal may decrease the risk of valvular insufficiency, thereby

decreasing the risk developing postthrombotic syndrome. 1–4

– Rapidly remove clot– Restore venous flow– Preserve valvular function– Identify and treat the cause of the thrombosis

• Valve function is preserved with rapid successful lytic therapy3

• Venous thrombectomy shows significant benefit vs anticoagulation in randomized trials1,4

1. Plate et al. J Vasc Surg. 1984;1:867–876. 2. Meissner et al. J Vasc Surg. 1993;18:596–602.3. Jeffrey et al. Proc 2nd Intl Vasc Sympos. 1989; London Abstract S20–3.4. Plate et al. Eur J Vasc Surg. 1990;4:483–489.

Thrombolytic Therapy for DVT

• Thrombolytic agent is delivered into thrombus using a drug infusion catheter

• Immediate restoration of Vein Patency

• Immediate Resolution of Patient Symptoms

• Preservation of Valve Function– Reduction in Recurrent DVT – Lower Likelihood of Postthrombotic Syndrome

Thrombolytic therapy is an adjunctive therapy to

anticoagulation, not a replacement

1100 Patency @ 1 yr Patency @ 1 yrIliacIliacFemoralFemoral

1100 Patency @ 1 yr Patency @ 1 yrIliacIliacFemoralFemoral

63%63%40%40%

63%63%40%40%

64%64%47%47%

64%64%47%47%

78%78%------------

78%78%------------

Iliac Stent: Patency @ 1 yr Iliac Stent: Patency @ 1 yr ++ StentStent-- StentStent

Iliac Stent: Patency @ 1 yr Iliac Stent: Patency @ 1 yr ++ StentStent-- StentStent

54%54%75%75%

54%54%75%75%

74%74%53%53%

74%74%53%53%

89%89%71%71%

89%89%71%71%

Initial SuccessInitial SuccessIliacIliacFemoralFemoral

Initial SuccessInitial SuccessIliacIliacFemoralFemoral

79%79% 63%63%40%40%

79%79% 63%63%40%40%

83%83% 64%64%47%47%

83%83% 64%64%47%47%

84%84% 78%78%------------

84%84% 78%78%------------

Bjarnason ‘97Bjarnason ‘97Bjarnason ‘97Bjarnason ‘97(n=77)(n=77)(n=77)(n=77)

Mewissen ‘99Mewissen ‘99Mewissen ‘99Mewissen ‘99(n=287)(n=287)(n=287)(n=287)

Comerota ‘01Comerota ‘01Comerota ‘01Comerota ‘01(n=58)(n=58)(n=58)(n=58)

Mewissen et alMewissen et alRadiol Radiol 19991999Mewissen et alMewissen et alRadiol Radiol 19991999

Bjarnason H et alBjarnason H et alJVIRJVIR 1997 1997Bjarnason H et alBjarnason H et alJVIRJVIR 1997 1997

Comerota et alComerota et alPhlebologyPhlebology 2001 2001Comerota et alComerota et alPhlebologyPhlebology 2001 2001

Contemporary Series: Bleeding Complications

Iliofemoral DVT – CD ThrombolysisIliofemoral DVT – CD Thrombolysis

Fatal PEFatal PE

Death 2Death 2°° LysisLysis

Fatal PEFatal PE

Death 2Death 2°° LysisLysis

0%0%

0%0%

0%0%

0%0%

0.2%0.2%

0.4%0.4%

0.2%0.2%

0.4%0.4%

0%0%

0%0%

0%0%

0%0% (? 2%)(? 2%)(? 2%)(? 2%)

Bjarnason ‘97Bjarnason ‘97Bjarnason ‘97Bjarnason ‘97(n=77)(n=77)(n=77)(n=77)

Mewissen ‘99Mewissen ‘99Mewissen ‘99Mewissen ‘99(n=287)(n=287)(n=287)(n=287)

Comerota ‘01Comerota ‘01Comerota ‘01Comerota ‘01(n=58)(n=58)(n=58)(n=58)

Bleeding complications < 5%in reports since 2001

Bleeding complications < 5%in reports since 2001

Contemporary Series: Bleeding Complications

Iliofemoral DVT – CD ThrombolysisIliofemoral DVT – CD Thrombolysis

Mewissen et alMewissen et alRadiol Radiol 19991999Mewissen et alMewissen et alRadiol Radiol 19991999

Bjarnason H et alBjarnason H et alJVIRJVIR 1997 1997Bjarnason H et alBjarnason H et alJVIRJVIR 1997 1997

Comerota et alComerota et alPhlebologyPhlebology 2001 2001Comerota et alComerota et alPhlebologyPhlebology 2001 2001

Pulm EmbPulm EmbPulm EmbPulm Emb 1%1% 1%1% 1%1%1%1% 0%0%0%0%

Major BleedMajor BleedMajor BleedMajor Bleed 5%5%5%5% 11%11%11%11% 9%9%9%9%

IC BleedIC BleedIC BleedIC Bleed 0%0%0%0% <1%<1%<1%<1% 0%0% 0%0%

• Trellis 8 clinical resultsO’Sullivan JVIR 2007; 18:715-724

• 19 Oncology patients with above knee DVT treated with Trellis with one year follow up.

• 96% of limbs showed Grade III and Grade II thrombus removal immediately post procedure

• Primary assisted patency rate of 100% at 30 days post procedure• Valvular function was maintained in 82% of treated lower extremities

(one year follow up) • Systemic thrombolysis was absent in patients tested for serum

fibrinogen levels or fibrin degradation products• All patients had an adjunctive procedure (PTV and/or venous

stenting)

Pharmaco-Mechanical Thrombolysis

• Combines thrombolytic infusion with mechanical energy

• Increases the surface area penetration of thrombolytics

• Dissolves and macerates thrombus

• Reduces the thrombolytic dose

• Reduces the time of thrombolytic infusion

• Reduces or eliminates patient time in the ICU

Patient Selection Patient with an expected long-term survival

Massive DVT or iliofemoral thrombophlebitis

Iliofemoral DVT

Multiple segment DVT

Patients who are symptomatic despite anticoagulation

Acute clot diagnosis: <14 DAYS

Isolated Thrombolysis Catheter –

Design and Components

Balloon Inflation & Thrombolytic Infusion Ports

8Fr Multi-LumenCatheter

Oscillation Drive Unit

Isolated Treatment Zone

Combination of Mechanical Motion & Drug Infusion

• Single-Setting Thrombolysis

• Targeted delivery of thrombolytic agents

• Treatment area isolated within occluding balloons

• Mechanical dispersion of infused thrombolytic agents

• Aspiration following treatment

Aspiration Port

Isolated Thrombolysis Catheter -

Thrombus Removal

Aspiration allows removal of residual vessel content

• Post-Operative Care:– Monitor Puncture Site and Dressings– Begin Standard Anti-Coagulation Therapy– Observe Patient for 4-8 Hours, Depending on Physician Orders

Isolated Thrombolysis Catheter –

Efficacy

• Mechanical “agitation” created by the drive wire– Combines mechanical action and thrombolytic infusion

– Greater drug dispersion

• Note: It may be important to treat thrombus as soon as possible– Ease of thrombus removal may decrease over time as clot ages.

Isolated Thrombolysis Catheter Potential for Improved Safety

Isolated treatment zone: Created by 2 Occlusion Balloons

Potential for lower lytic utilization Reduced treatment time

Procedure TimeDosage

(t-PA)

Catheter Directed

Thrombolysis

2-6 days

0.5mg/hr

(24mg / 2 days)

Isolated Thrombolysis

2 hours3-5mg

(per segment)

Isolated Thrombolysis Catheter –

TRELLIS Venograms

Full occlusion in common femoral through iliac veinsFull occlusion in common femoral through iliac veins

Patency restored throughout treated areasPatency restored throughout treated areas

Isolated Thrombolysis Catheter

Symptom Relief

Pain and swelling caused by iliofemoral DVT

Reduced swelling following Isolated Thrombolysis

May Thurner Syndrome(Iliac Vein Compression)

Iliofemoral Vein ThrombusCase Study

Iliac/Femoral Vein with Iliac/Femoral Vein with Acute on Chronic Acute on Chronic

ThrombusThrombusIliac Vein Subacute ThrombusIliac Vein Subacute Thrombus

Final FilmFinal Film

DVT also occurs in the arm

Thoracic outlet syndromePaget Schroeder syndrome

Chronic catheterizationDialysis access

Trauma

Subclavian DVTCase Study

BeforeBefore AfterAfter

Subclavian Thrombus Removed

Isolated Thrombolysis Catheter -

Benefits For All• Isolated Thrombolysis:

– Pharmaco-Mechanical system aids in rapid thrombus removal – Restores vessel patency– Minimizes drug exposure

• Patient:– More immediate symptomatic relief– Decreased risk of Post-Thrombotic Disease (PTS)– Potential for NO ICU Stay and overall shorter length of stay– Single setting treatment of DVT

• Physician & Staff:– 1.5 to 2 hour procedure– Easier post-up care– Elimination of repeat venograms

• Hospital:– Decreased Procedural Costs:

• $2,000-$3,000 Per DVT Patient

– Decreased ICU Costs• $4,000-12,000 Savings per DVT Patient

The Evolution of DVT Treatment

DVT Management Strategy

Anticoagulation/Lysis Risk Assessment*

PMT

Temporary IVC Filter Anticoagulation

IVC and/or Iliofemoral Femoral/Popliteal Isolated Calf

Symptomatic Asymptomatic

Unstable Thrombus?

Compression HoseAnticoagulation

Follow-up

Compression Hose

Consider Hypercoagulability Work-up

Yes

No

Follow-up

Lytic Contraindications? Isolated PMT*

Correct Underlying Stenosis

Therapeutic Goals of DVT Treatment

Relieve Patient Symptoms

Prevent Pulmonary Embolism

Prevent Further Thrombus Propagation

Prevent DVT Recurrence

Maintain Valve Competence

Prevent Postthrombotic Syndrome

Early Intervention =Quality of Life Improvement